ABSTRACT The few studies on Alzheimer's disease (AD) in American Indians (AIs) are limited by small, single- community samples. The only available prevalence estimate was based on 1 probable case detected among 192 Cree elders. Data on AD risk factors in AIs derive primarily from a study that assessed 39 Choctaw patients with AD. Further limiting our knowledge is the underrepresentation of AIs in the AD Research Centers: 250 of 32,479 (0.8%) participants are AI,in contrast to their share of the US population (~1.7%). A review by NIA stated, ?Accurate reflection of the prevalence of AD in AI communities awaits a study with adequate sampling of the population.? The Strong Heart Study and its ancillary project, the Strong Heart Stroke Study (SHSS), provide the best existing resource for researching AD in AIs. The Strong Heart Study conducted exams from 1989-1990, enrolling 4,549 people from tribes in the Southwest (Arizona), Southern Plains (Oklahoma), and Northern Plains (North and South Dakota). Follow-up exams conducted from 1993-2000 revealed disproportionate burdens of many AD risk factors. From 2010-2013, the SHSS administered physical examinations, cognitive tests, and structural brain magnetic resonance imaging (MRI) to 1,033 surviving Strong Heart Study participants to investigate vascular brain injury and its manifestations in elderly AIs. The Satellite Core of the University of Washington AD Research Center is funded to repeat the SHSS exams in 100 participants from the Southern Plains field site. These individuals are a subset of the 450 participants from all 3 sites who we expect could participate in follow-up exams over the next 4 years. In this Revision, we will expand the funded Satellite Core to re-examine the remaining 350 SHSS participants, and assemble a dataset that will position us to estimate AD prevalence and risk factors in the entire cohort. We will augment these data with functional MRI, which is only available at the Southwest site. Our Specific Aims are to: 1) Repeat cognitive function tests, document changes by age and sex, and add Uniform Data Set components; 2) Repeat standard blood tests for vascular brain injury risk factors and obtain samples for future biomarker and genetic research that could be accessed (with proper approvals) through the Clinical Core; 3) Capitalize on the adjudication processes established by the Clinical Core to estimate AD and MCI prevalence; 3) Incorporate data from 3-dimensional volumetric brain mapping and functional MRI for Southwest participants to enable more sensitive and specific evaluation of AD; 4) Work with the Outreach, Recruitment, and Education Core to raise awareness of AD and provide education to all SHSS tribes. This effort will be a major step towards remediating AD knowledge gaps and facilitating AD research in AI people.